[Idiopathic Progressive Subglottic Stenosis: Surgical Techniques]. / Idiopathische progressive subglottische Stenose - chirurgische Therapieoptionen.

Idiopathic subglottic stenosis is a disease characterized by slow, progressive scarring and constriction of the subglottic airway. It almost always occurs in females between the 3rd and 5th decade of life. Symptoms are frequently misinterpreted as asthma and patients are referred for endoscopic evaluation only when asthma medications fail to alleviate their symptoms. Treatment options can be divided into endoscopic and open surgical techniques. Microlaryngoscopic scar reduction by laser followed by balloon dilation usually delivers good short-term results. However, the majority of patients will experience restenosis within a short period of time. Open surgical correction techniques are based on a complete removal of the affected airway segment. This must be combined with various extended resection techniques in patients with advanced stenosis. Depending on the extent and severity of the stenosis the following surgical techniques are required: standard cricotracheal resection (Grillo's technique), cricoplasty with dorsal and lateral mucosaplasty, or a combination of resection and enlargement techniques using rib cartilage grafts. In experienced centres, success rates of over 95 % are reported with good functional outcome of voice and deglutition.

Secretome of apoptotic peripheral blood cells (APOSEC) attenuates microvascular obstruction in a porcine closed chest reperfused acute myocardial infarction model: role of platelet aggregation and vasodilation.

Although epicardial blood flow can be restored by an early intervention in most cases, a lack of adequate reperfusion at the microvascular level is often a limiting prognostic factor of acute myocardial infarction (AMI). Our group has recently found that paracrine factors secreted from apoptotic peripheral blood mononuclear cells (APOSEC) attenuate the extent of myocardial injury. The aim of this study was to determine the influence of APOSEC on microvascular obstruction (MVO) in a porcine AMI model. A single dose of APOSEC was intravenously injected in a closed chest reperfused infarction model. MVO was determined by magnetic resonance imaging and cardiac catheterization. Role of platelet function and vasodilation were monitored by means of ELISA, flow cytometry, aggregometry, western blot and myographic experiments in vitro and in vivo. Treatment of AMI with APOSEC resulted in a significant reduction of MVO. Platelet activation markers were reduced in plasma samples obtained during AMI, suggesting an anti-aggregatory capacity of APOSEC. This finding was confirmed by in vitro tests showing that activation and aggregation of both porcine and human platelets were significantly impaired by co-incubation with APOSEC, paralleled by vasodilator-stimulated phosphoprotein (VASP)-mediated inhibition of platelets. In addition, APOSEC evidenced a significant vasodilatory capacity on coronary arteries via p-eNOS and iNOS activation. Our data give first evidence that APOSEC reduces the extent of MVO during AMI, and suggest that modulation of platelet activation and vasodilation in the initial phase after myocardial infarction contributes to the improved long-term outcome in APOSEC treated animals.

Differential expression of circulating miRNAs after alemtuzumab induction therapy in lung transplantation.

Alemtuzumab is a monoclonal antibody targeting CD52, used as induction therapy after lung transplantation (LTx). Its engagement produces a long-lasting immunodepletion; however, the mechanisms driving cell reconstitution are poorly defined. We hypothesized that miRNAs are involved in this process. The expression of a set of miRNAs, cytokines and co-signaling molecules was measured with RT-qPCR and flow cytometry in prospectively collected serum samples of LTx recipients, after alemtuzumab or no induction therapy. Twenty-six LTx recipients who received alemtuzumab and twenty-seven matched LTx recipients without induction therapy were included in the analysis. One year after transplantation four miRNAs were differentially regulated: miR-23b (p = 0.05) miR-146 (p = 0.04), miR-155 (p < 0.001) and miR-486 (p < 0.001). Expression of 3 miRNAs changed within the alemtuzumab group: miR-146 (p < 0.001), miR-155 (p < 0.001) and miR-31 (p < 0.001). Levels of IL-13, IL-4, IFN-γ, BAFF, IL-5, IL-9, IL-17F, IL-17A and IL-22 were different one year after transplantation compared to baseline. In no-induction group, concentration of sCD27, sB7.2 and sPD-L1 increased overtime. Expression of miR-23b, miR-146, miR-486, miR-155 and miR-31 was different in LTx recipients who received alemtuzumab compared to recipients without induction therapy. The observed cytokine pattern suggested proliferation of specific B cell subsets in alemtuzumab group and co-stimulation of T-cells in no-induction group.

High levels of lung resident CD4+CD28null cells in COPD: implications of autoimmunity.

Chronic obstructive pulmonary disease (COPD) is a worldwide burden and a major cause of death. Pathogenetic mechanisms underlying the disease are still largely unknown. However, a continuous toxic injury due to tobacco smoking leading to a self-maintaining inflammatory process is considered a key factor in the pathophysiology of the disease. Evidence that autoimmunity might be involved in the maintenance of COPD has been recently noticed with great interest.During the chronic phase of an autoimmune response, lymphocytes lose their costimulatory signals. Previously, CD4+CD28null cells were reported to be systemically heightened in COPD patients. However, a direct role of CD4+CD28null cells in the pathogenesis of COPD is still under discussion, since there is no evidence that CD4+CD28null cells originate from the lungs of diseased patients. Therefore, we evaluated lungs from end-stage COPD patients and compared the levels of tissue infiltrating CD4+CD28null cells to systemic levels. We could show that CD4+CD28null cells are present in high amounts in lung tissue obtained from COPD GOLD IV patients suggesting a direct involvement of those cells in the pathophysiology of COPD. Furthermore, purified lung-resident CD4+ cells showed a stable proliferative response to lung specific elastin and collagen.These results further corroborate the role of autoreactive CD4+ cells in the maintenance of the inflammatory destruction in COPD. Modulating CD4+ cell function might be a new promising tool for future therapeutic approaches.